Possible Hypothesis on Alzheimer’s Disease Pathogenesis and Its Link to Trisomy 21

Abstract

The presence of “plaques” and “tangles” in the brain is considered as the hallmark of Alzheimer’s disease. The major constituent of the plaques is a protein (“A-beta”) which is split off from a much larger parent protein called Amyloid Precursor Protein (APP), and that of tangles is the protein tau, which normally functions to stabilize microtubules within neuronal axons. There are several possibilities that elaborate the change in amyloid formation and its consequences on the neuronal death to bring AD; the first is the amyloid cascade hypothesis that describes how early-onset AD is induced by mutations in APP, the presenilins and apoE4. The second possibility is the calcium hypothesis of Alzheimer’s disease, which argues the calcium-induced memory loss in Alzheimer’s disease. Mapping of the gene that encodes the precursor protein (APP) of the β-amyloid (Aβ) present in the Aβ plaques in both AD and DS to chromosome 21 was strong evidence that the chromosome 21 gene product was a principal neuropathogenic culprit in the AD as well as DS. The main objective of this review was elucidate the possible hypothesis of Alzheimer’s disease and to pinpoint the chromosome 21 gene product as principal neuropathogenic culprit in the pathogenesis of AD and DS. Different articles on pathogenesis of AD and its link to DS were revised. As conclusion, different hypothesis on AD pathogenesis discussed on this review illustrated well about the pathogenesis of AD, its link to DS and potential target for certain therapeutic agents to act on the treatment of AD and DS.